The protective role of erythropoietin against doxorubicin-induced cardiomyopathy
Bibliographic record
Abstract
9555 Background: The clinical usage of antineoplastic drug doxorubicin (DOX) is limited due to apoptosis-related cardiotoxic side effects. The cytokine erythropoietin (EPO) is critical for the production of mature red blood cells and is commonly used to treat anemia in cancer therapy. Recent experimental data report that EPO contributes to anti-apoptosis in neuronal, vascular smooth muscle, and vascular endothelial cells. Methods: To assess whether EPO protects the heart against DOX-induced cardiomyopathy, EPO (1U/mL) was applied to cultured neonatal mouse ventricular myocytes (NMVM). Results: EPO protected (P<0.05) NMVMs against DOX application (0.1, 0.5 & 1.0μM) - induced cytotoxic cell death (by ≈50%) and apoptosis as measured by DNA fragmentation and caspase-3 activity (reduced from 44.5±6.2 nmol pNA/mg to 31.5±6.1). This protection by EPO correlated with increased (P<0.05) phosphorylation of PI3K-dependent survival pathways, Akt/PKB (∼2-fold) and GSK-3β (∼1.3-fold), which was blocked by the PI3K inhibitor LY294002. LY294002 also diminished EPO’s protective effects on cell survival and caspase-3 activity (45.5±8.9 nmol pNA/mg in DOX+EPO+LY294002), suggesting that EPO’s protection is mediated by PI3K-dependent pathways. These protective actions of EPO (2,000U/kg/wk) were also observed in mice administered DOX (3 weekly i.p. injections of 5mg/kg) wherein cardiac function, as assessed by fractional shortening (FS) using echocardiography (FS = 50.9±5% for DOX+EPO vs. 33.0±0.2% for DOX+Placebo). Conclusions: This study suggests that EPO protects myocardium against DOX-induced cell death and apoptosis via PI3K-dependent pathways as well as impaired heart function. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration University of Toronto
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".